1. Field of the Invention
This invention relates to an improved dosage form for ophthalmic drugs. More particularly, it relates to a new ocular dosage form which is easy to use and which achieves a controlled release of drug to the the eye over a prolonged period of time.
2. The Prior Art
Most ocular treatments call for the administration of medicaments topically to the tissues of the ocular cavity. These medicaments have, in the prior art, assumed a wide range of forms. The most common dosage form for ophthalmic medicaments is liquid drops. Liquid drops may be found for example, in over-the-counter ocular decongestants and in anti-glaucoma solutions, such as 1/2%, 1% or 2% aqueous solutions of pilocarpine salts. The liquid drop dosage form is easy to use, but suffers from the inherent disadvantage that the medication it contains is rapidly washed from the ocular cavity by tear flow. Thus, for drops, a continuous sustained level of medication is not achieved. Attempts to achieve sustained levels include periodic application of drops, but this results in the eye receiving a massive and unpredictable amount of medication. The result of this administration and washing is that the level of medication surges to a peak at the time the drops are applied, then the drug concentration falls rapidly. A plot of medication concentration in the eye versus time has the appearance of a series of peaks of drug level which may surpass the toxic threshold of the drug separated by extended valleys of drug level below the critical level needed to achieve the desired therapeutic effect.
Suspensions of particles of drug in liquids have been widely used as well; for example, hydrocortisone acetate and prednisolone acetate are typical of drugs presently marketed as suspensions. These suspensions usually contain preservatives, isotonicity adjusters, and suspending and dispersing agents. Present day suspensions create a variety of problems. First, they generally may only be made with relatively water-insoluble drugs, since soluble drugs form saturated solutions which have higher tonicities than the eye can easily adapt to. Also, the rate of release from the particles of the suspension is related to the rate of solubility of the drug so that one dosage rate alone may be obtained with a given drug. In the majority of cases, this one rate of delivery is not ideal.
Other dosage forms have been proposed, most on the basis that seemingly they give a more prolonged release of drug to the eye. These dosage forms include ointments, lamellae of glycerinated gelatin, such as described in U.S. Pat. No. 273,410 issued Mar. 6, 1883, and other similar dosage forms. These dosage forms give an only marginally more sustained drug release than do liquid drops, and most particularly, do not give a constant release pattern; additionally, they suffer the disadvantages of being difficult to sterilize and apply, and often cause blurring of vision.
Recently developed ophthalmic drug delivery systems, such as described in U.S. Pat. No. 3,416,530 issued Dec. 17, 1968 and in U.S. Pat. No. 3,618,604 issued Nov. 9, 1971, do give true controlled deliveries of drug. The ophthalmic drug delivery systems of these patents are unitary ocular inserts, several millimeters in size which are placed in the upper or lower sac of the eye to delivery a complete ophthalmic dosage regimen for a period of 24 hours or longer. While these ocular inserts do deliver drug to the eye continuously, and in a controlled manner, there remains improvements to be made. Many patients, especially the farsighted elderly, have difficulty inserting or removing ocular inserts. Also, the large unitary ocular inserts are at times accidentally ejected from the ocular cavity by the blinking action of the eyelids.
In view of the above presentation, it becomes immediately apparent that it would indeed be desirable to provide an ophthalmic dosage form which makes available to the art the ease of administration of liquid drops combined with the drug release characteristics of ocular inserts to improve the administration of ocular drugs.